review · International Journal of Molecular Sciences
Many patients treated for early breast cancer experience disease recurrence caused by subclinical minimal residual disease. Circulating tumour DNA and circulating tumour cells obtained via liquid biopsy provide minimally invasive means to detect this residual disease following treatment. A systematic review and meta-analysis of seventeen studies covering over three thousand patients evaluated the prognostic value of both biomarkers. Detection of circulating tumour cells after treatment was significantly linked to reduced survival. However, presence of circulating tumour DNA displayed a considerably stronger prognostic impact, particularly when evaluated after adjuvant rather than neoadjuvant therapy. While both biomarkers reliably signal residual disease, none of the included studies compared both indicators within the same patient group. Prospective randomised trials are still required to assess whether adjusting treatment based on these liquid biopsy findings can improve clinical outcomes.
Identifying early breast cancer patients at high risk of relapse remains a major clinical challenge. Blood-based liquid biopsies offer a way to detect trace residual cancer without invasive tissue sampling. Demonstrating that circulating tumour DNA strongly predicts survival helps clinicians identify which post-treatment monitoring tools provide the clearest signals for recurrence, guiding future approaches to personalised cancer care.
The findings support the clinical utility of liquid biopsy assays, particularly circulating tumour DNA tests, for post-treatment monitoring in early breast cancer. Diagnostic developers and oncology clinicians could use these tools to identify patients needing closer surveillance or altered therapy. However, the evidence remains at an evaluative research stage, and commercial implementation in treatment decision-making requires prospective randomised clinical trials to validate biomarker-guided intervention strategies.
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Despite advances in systemic therapy, many early breast cancer patients experience recurrence due to subclinical minimal residual disease (MRD). Circulating tumor DNA (ctDNA) and circulating tumor cells (CTCs) have emerged as promising liquid biopsy markers for post-treatment MRD detection. This pre-registered systematic review and meta-analysis (PROSPERO/PRISMA 2020) evaluated their comparative prognostic significance. Seven databases were searched from inception to March 2026. Eligible studies included early breast cancer patients undergoing post-treatment ctDNA or CTC assessment after neoadjuvant or adjuvant therapy, reporting survival outcomes with extractable hazard ratios. Quality was assessed using the QUIPS tool; random-effects meta-analyses used the REML estimator. Seventeen studies (thirteen ctDNA, four CTCs; n = 3030) were included. Post-treatment CTC positivity was significantly associated with poorer survival (pooled HR = 2.99, 95% CI: 1.99–4.49; I2 = 17.2%). ctDNA positivity demonstrated a substantially stronger prognostic effect (pooled HR = 10.28, 95% CI: 6.32–16.70; I2 = 47.3%). Subgroup analyses identified assessment timing as a key heterogeneity source, with stronger effects after adjuvant (HR = 20.62; k = 4) versus neoadjuvant therapy (HR = 6.07; k = 9); given the small number of post-adjuvant studies, this finding is hypothesis-generating. No significant publication bias was detected. Both markers were significant prognostic markers of MRD. ctDNA showed a stronger pooled prognostic association, although no study assessed both biomarkers within the same cohort and direct head-to-head comparisons therefore remain lacking. Prospective randomized trials are needed to evaluate MRD-guided treatment strategies.
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DOI: 10.3390/ijms27177719
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